Moderate associations between the use of levonorgestrel-releasing intrauterine device and metabolomics profile

J Clin Endocrinol Metab. 2024 May 8:dgae318. doi: 10.1210/clinem/dgae318. Online ahead of print.

Abstract

Context: Use of levonorgestrel-releasing intrauterine device (LNG-IUD) has become common irrespective of age and parity. To date, only a few studies have examined its possible metabolic changes and large-scale biomarker profiles in detail and in a longitudinal design.

Objective: To apply the metabolomics technique to examine the metabolic profile associated with the use of LNG-IUD both in a cross-sectional and in a longitudinal design.

Design: The study consists of cross-sectional and longitudinal analyses of a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). All participants aged 18-49 years with available information on hormonal contraceptive use and metabolomics data (n=1767) were included. Altogether 212 metabolic measures in LNG-IUD users (n=341) were compared to those in non-users of hormonal contraception (n=1426) via multivariable linear regression models. Participants with complete longitudinal information (n=240) were divided into continuers, stoppers, starters, and never-user groups, and 11-year changes in levels of each metabolite were compared.

Results: After adjustment for covariates, levels of 102 metabolites differed in LNG-IUD current users compared to non-users of hormonal contraception (median difference in biomarker concentration: -0.12 SD): lower levels of fatty acids concentrations and ratios, cholesterol, triglycerides and other lipids, as well as particle concentration, cholesterol, total lipids and phospholipids in lipoproteins. The 11-year metabolic changes did not differ in relation to changes in LNG-IUD use.

Conclusions: The use of LNG-IUD was associated with several moderate metabolic changes, mostly suggestive of a reduced arterial cardiometabolic risk. Changes in LNG-IUD use were not related to long-term metabolic changes.

Keywords: cardiometabolic risk; fertile-aged; levonorgestrel-releasing intrauterine device; longitudinal; metabolic changes; metabolites.